This application integrates several scientific disciplines, basic biomedicine, epidemiology, ecology and engineering to assess the impact of hazardous waste exposure on human health. The biomedical portion of the Program Project seeks to develop new and sensitive methods for detecting human exposure to chemicals. This portion focuses on assays that have been previously developed as research tools, and which show promise for the detection of low level environmental exposure in humans. The tissues to be monitored include blood, hair follicle cells, urine and other tissues available by non-invasive sampling methods. In the early stages of the Program Project, experimental animals were utilized to test the specificity, sensitivity and validity of the methods for monitoring in vivo human exposures. Animals were exposed by inhalation, ingestion and by other routes to mimic human exposure to toxic Superfund chemicals. During the renewal of this project greater emphasis will be placed upon the application of the biomarker assays in assessing human exposure, although animal validation will still be continued. The assays under development are proposed to be indicators of toxic metal exposure, and include those that measure oxidative stress, proliferation, RNA expression, and the complexing of protein to DNA in lymphocytes, proliferation and viability of skin keratinocytes and skin fibroblasts, and neurobehavioral changes. This Program Project is strongly focused on metals, particularly chromium and cadmium. It also focuses on two toxic waste dump sites: Foundry Cove which is contaminated predominantly with cadmium and nickel; and Jersey City, NJ which is predominantly a chromium dump site. These sites are both likely to be sources of human exposure, and human sampling will be carried out under the direction of the Epidemiology Core. The Engineering and Ecology Components are integrated to understand the impact of cadmium, chromium and other heavy metal contaminants in the environment, in terms of movement from Superfund sites to accumulation in the food chain leading to human exposures.